1. Field of the Invention
The present invention relates generally to a sensing device for use in a binding assay for detecting the presence of an analyte and more particularly to a sensing device having a magnetic sensing element that responds to the radial fringing field of a magnetic particle.
2. Description of the Background Art
Binding assays such as immunoassays, DNA hybridization assays, and receptor-based assays are widely used in the medical community as diagnostic tests for a wide range of target molecules or analytes. Binding assays exploit the ability of certain molecules, herein referred to as xe2x80x9cspecific binding membersxe2x80x9d, to specifically bind target molecules. Specific binding members such as antibodies, strands of polynucleic acids (DNA or RNA) and molecular receptors, are capable of selectively binding to (xe2x80x9crecognizingxe2x80x9d) potential target molecules such as polynucleic acids, enzymes and other proteins, polymers, metal ions, and low molecular weight organic species such as toxins, illicit drugs, and explosives. In a solid phase assay, a recognition event causes binding members in a fluid test medium to become immobilized with respect to a solid substrate in relation to the amount of analyte present in the medium.
Typically, because of the small size of the molecules involved, recognition events in a binding assay cannot be observed directly. This problem is overcome through the use of labeled binding molecules, which indicate their presence through the generation of a measurable signal. Various types of binding assays have been devised that use radioactive, fluorescent, chemiluminescent, or enzymatic labels.
Binding assays that use magnetic particles as labels have been described. Various means have been described for detecting the magnetic particles.
For example, Baselt, D. R. et al, xe2x80x9cBiosensor Based on Force Microscope Technologyxe2x80x9d, J. Vac. Sci. Technol. B, vol. 14, no. 2, pp. 789-793, (1996) and U.S. Pat. No. 5,807,758 to Lee et al, incorporated herein by reference, describe a magnetic force sensor called a Force Amplified Biological Sensor (FABS) that uses a cantilever-beam force transducer to measure the total magnetic force exerted by adhering magnetic particles when a magnetic field is applied.
U.S. Pat. Nos. 5,445,970 and 5,445,971 to Rohr, incorporated herein by reference, describe a device that uses a microbalance, rather than a cantilever-beam force transducer, to measure the force exerted by adhering magnetic particles when a magnetic field is applied. Assay methods involving the measurement of force exerted by adhering magnetic particles when a magnetic field is applied are described in U.S. Pat. No. 5,998,224 to Rohr.
R. Kotitz et al. (41st annual conference on Magnetism and Magnetic Materials, November 1996; see abstract book p. 73), incorporated herein by reference, describes a binding assay that uses a Superconducting Quantum Interference Device (SQUID) to detect whether magnetic particles have been immobilized by biological recognition events on the side of a test tube.
U.S. Pat. No. 5,981,297 to Baselt, incorporated herein by reference, describes a binding assay method and apparatus for detecting magnetized particles by monitoring a magnetoresistive or magnetostrictive response of a magnetic field sensor to the magnetized particles.
The orientation of the moment of a magnetizable particle is generally defined by the direction of an external magnetic field applied to the particle. If that field is applied perpendicular to the plane of a magnetic field sensor (in order to avoid affecting the moments in the plane of magnetic layers), the magnetic fringing field from the particle exhibits a circularly symmetric pattern centered on the particle axis. This field contains both radial components in the plane of the sensor and components perpendicular to the plane of the sensor. In the embodiments disclosed in U.S. Pat. No. 5,981,297, the magnetoresistive sensing elements are in the form of thin film magnetoresistive strips. Typically, such magnetoresistive sensing elements have a rectilinear symmetry and uniaxial sensitivity to magnetic fields. These sensing elements respond primarily to perpendicular components of the magnetic fringing field of a magnetic particle and not to the radial components. Thus, the full usefulness of a magnetic particle in generating a detectable signal is not exploited.
Accordingly, it is an object of this invention to maximize the ability of a magnetic sensing element to detect an attached magnetic particle.
It is another object of the present invention to provide a magnetic sensing element that effectively uses the radial components of the fringing field generated by a magnetized magnetic particle attached to the sensor element to produce a detectable signal.
These and other objects are accomplished by a sensing device that includes a magnetic sensing element that has at least one planar layer of electrically conductive ferromagnetic material that has an initial state in which the material has a circular magnetic moment within the plane of the layer. The magnetic sensing element has molecules of a first specific binding member attached to it. The device also includes a fluid test medium to which the magnetic sensing element is exposed during the course of the assay. The fluid test medium includes magnetizable particles that become immobilized during the assay in relation to the amount of analyte in the test medium. The relative size of the magnetic particle and the magnetic sensing element and the location of the molecules of the first specific binding member on the magnetic sensing element are selected so that when the magnetic particle becomes immobilized with respect to the magnetic sensing element, the radial fringing field of the magnetic particle causes the magnetic moment of at least one layer of electrically conductive ferromagnetic material to shift from circular to radial, thereby causing a detectable change in the electrical resistance of the magnetic sensing element.
The invention further relates a method of detecting an analyte in a test sample using the apparatus described above.